Simulation study on the validity of the average risk approach in estimating population attributable fractions for continuous exposures.

BACKGROUND: The population attributable fraction (PAF) is an important metric for estimating disease burden associated with causal risk factors. In an International Agency for Research on Cancer working group report, an approach was introduced to estimate the PAF using the average of a continuous exposure and the incremental relative risk (RR) per unit. This 'average risk' approach has been subsequently applied in several studies conducted worldwide. However, no investigation of the validity of this method has been done. OBJECTIVE: To examine the validity and the potential magnitude of bias of the average risk approach. METHODS: We established analytically that the direction of the bias is determined by the shape of the RR function. We then used simulation models based on a variety of risk exposure distributions and a range of RR per unit. We estimated the unbiased PAF from integrating the exposure distribution and RR, and the PAF using the average risk approach. We examined the absolute and relative bias as the direct and relative difference in PAF estimated from the two approaches. We also examined the bias of the average risk approach using real-world data from the Canadian Population Attributable Risk of Cancer study. RESULTS: The average risk approach involves bias, which is underestimation or overestimation with a convex or concave RR function (a risk profile that increases more/less rapidly at higher levels of exposure). The magnitude of the bias is affected by the exposure distribution as well as the value of RR. This approach is approximately valid when the RR per unit is small or the RR function is approximately linear. The absolute and relative bias can both be large when RR is not small and the exposure distribution is skewed. CONCLUSIONS: We recommend that caution be taken when using the average risk approach to estimate PAF.

Estimating the future cancer management costs attributable to modifiable risk factors in Canada.

OBJECTIVES: An estimated 33-37% of incident cancers in Canada are attributable to modifiable risk factors. Interventions targeting these risk factors would minimize the substantial health and economic burdens Canadians face due to cancer. We estimate the future health and economic burden of cancer in Canada by incorporating data from the Canadian Population Attributable Risk of Cancer (ComPARe) study into OncoSim, a web-based microsimulation tool. METHODS: Using the integrated OncoSim population attributable risk and population impact measures, we evaluated risk factor-targeted intervention scenarios implemented in 2020, assuming the targeted risk factor prevalence reduction would be achieved by 2032 with a 12-year latency period. RESULTS: We estimate that smoking will be the largest contributor to cancer-related costs, with a cost of CAD $44.4 billion between 2032 and 2044. An estimated CAD $3.3 billion of the cost could be avoided with a 30% reduction in smoking prevalence by 2022. Following smoking, the next highest cancer management costs are associated with inadequate physical activity and excess body weight, accounting for CAD $10.7 billion ($2.7 billion avoidable) and CAD $9.8 billion ($3.2 billion avoidable), respectively. Avoidable costs for other risk factors range from CAD $90 million to CAD $2.5 billion. CONCLUSION: Interventions targeting modifiable cancer risk factors could prevent a substantial number of incident cancer cases and billions of dollars in cancer management costs. With limited budgets and rising costs in cancer care in Canada, these simulation models and results are valuable for researchers and policymakers to inform decisions and prioritize and evaluate intervention programs.

RéSUMé: OBJECTIFS: Il est estimé que de 33 % à 37 % des cancers incidents au Canada sont imputables à des facteurs de risque modifiables. Des interventions ciblant ces facteurs de risque réduiraient le fardeau sanitaire et économique considérable du cancer dans la population canadienne. Nous avons estimé le futur fardeau sanitaire et économique du cancer au Canada en intégrant les données de l'étude ComPARe (Canadian Population Attributable Risk of Cancer) dans l'outil de microsimulation en ligne OncoSim. MéTHODE: À l'aide des indicateurs d'impact dans la population et du risque attribuable dans la population intégrés dans OncoSim, nous avons évalué des scénarios d'intervention mis en œuvre en 2020 axés sur les facteurs de risque, en partant de l'hypothèse que la réduction de la prévalence des facteurs de risque ciblés serait atteinte d'ici 2032 avec une période de latence de 12 ans. RéSULTATS: Nous estimons que le tabagisme sera le facteur qui contribuera le plus aux coûts du cancer, avec un coût de 44,4 milliards $ CA entre 2032 et 2044. Il est estimé qu'une part de 3,3 milliards $ CA de ce coût pourrait être évitée en réduisant de 30 % la prévalence du tabagisme d'ici 2022. Après le tabagisme, les coûts de prise en charge du cancer les plus élevés sont associés à l'inactivité physique et au surpoids, qui représentent respectivement 10,7 milliard $ CA (dont 2,7 milliards $ évitables) et 9,8 milliards $ CA (dont 3,2 milliards $ évitables). Les coûts évitables pour d'autres facteurs de risque vont de 90 millions $ CA à 2,5 milliards $ CA. CONCLUSION: Des interventions ciblant les facteurs de risque de cancer modifiables pourraient prévenir un nombre considérable de cas de cancers incidents et épargner des milliards de dollars en coûts de prise en charge du cancer. Avec les budgets serrés et la hausse des coûts des soins du cancer au Canada, ces modèles de simulation et leurs résultats permettent aux chercheurs et aux responsables des politiques d'éclairer les décisions et de hiérarchiser et d'évaluer les programmes d'intervention.

Association of worker characteristics and early reimbursement for physical therapy, chiropractic and opioid prescriptions with workers' compensation claim duration, for cases of acute low back pain: an observational cohort study.

OBJECTIVE: To assess the association between early reimbursement for physiotherapy, chiropractic and opioid prescriptions for acute low back pain (LBP) with disability claim duration. DESIGN: Observational cohort study. SETTING AND PARTICIPANTS: From a random sample of 6665 claims for acute, uncomplicated LBP approved by the Ontario Workplace Safety and Insurance Board (WSIB) in 2005, we analysed 1442 who remained on full benefits at 4 weeks after claim approval. PRIMARY OUTCOME MEASURE: Our primary outcome was WSIB claim duration. RESULTS: We had complete data for all but 3 variables, which had <15% missing data, and we included missing data as a category for these factors. Our time-to-event analysis was adjusted for demographic, workplace and treatment factors, but not injury severity, although we attempted to include a sample with very similar, less-severe injuries. Regarding significant factors and treatment variables in our adjusted analysis, older age (eg, HR for age ≥ 55 vs <25=0.52; 99% CI 0.36 to 0.74) and WSIB reimbursement for opioid prescription in the first 4 weeks of a claim (HR=0.68; 99% CI 0.53 to 0.88) were associated with longer claim duration. Higher predisability income was associated with longer claim duration, but only among persistent claims (eg, HR for active claims at 1 year with a predisability income >$920 vs ≤$480/week=0.34; 99% CI 0.17 to 0.68). Missing data for union membership (HR=1.27; 99% CI 1.01 to 1.59), and working for an employer with a return-to-work programme were associated with fewer days on claim (HR=1.78; 99% CI 1.45 to 2.18). Neither reimbursement for physiotherapy (HR=1.01; 99% CI 0.86 to 1.19) nor chiropractic care (HR for active claims at 60 days=1.15; 99% CI 0.94 to 1.41) within the first 4 weeks was associated with claim duration. Our meta-analysis of 3 studies (n=51,069 workers) confirmed a strong association between early opioid use and prolonged claim duration (HR=0.57, 95% CI 0.48 to 0.69; low certainty evidence). CONCLUSIONS: Our analysis found that early WSIB reimbursement for physiotherapy or chiropractic care, in claimants fully off work for more than 4 weeks, was not associated with claim duration, and that early reimbursement for opioids predicted prolonged claim duration. Well-designed randomised controlled trials are needed to verify our findings and establish causality between these variables and claim duration.

Association of psychotherapy with disability benefit claim closure among patients disabled due to depression.

BACKGROUND: Depression is the most frequent reason for receiving disability benefits in North America, and treatment with psychotherapy is often funded by private insurers. No studies have explored the association between the provision of psychotherapy for depression and time to claim closure. METHODS: Using administrative data from a Canadian disability insurer, we evaluated the association between the provision of psychotherapy and short-term disability (STD) and long-term disability (LTD) claim closure by performing Cox proportional hazards regression. RESULTS: We analyzed 10,508 STD and 10,338 LTD claims for depression. In our adjusted analyses, receipt of psychotherapy was associated with longer time to STD closure (HR [99% CI] = 0.81 [0.68 to 0.97]) and faster LTD claim closure (1.42 [1.33 to 1.52]). In both STD and LTD, older age (0.90 [0.88 to 0.92] and 0.83 [0.80 to 0.85]), per decade), a primary diagnosis of recurrent depression versus non-recurrent major depression (0.78 [0.69 to 0.87] and 0.80 [0.72 to 0.89]), a psychological secondary diagnosis (0.90 [0.84 to 0.97] and 0.66 [0.61 to 0.71]), or a non-psychological secondary diagnosis (0.81 [0.73 to 0.90] and 0.77 [0.71 to 0.83]) versus no secondary diagnosis, and an administrative services only policy ([0.94 [0.88 to 1.00] and 0.87 [0.75 to 0.996]) or refund policy (0.86 [0.80 to 0.92] and 0.73 [0.68 to 0.78]) compared to non-refund policy claims were independently associated with longer time to claim closure [corrected]. CONCLUSIONS: We found, paradoxically, that receipt of psychotherapy was independently associated with longer time to STD claim closure and faster LTD claim closure in patients with depression. We also found multiple factors that were predictive of time to both STD and LTD claim closure. Our study has limitations, and well-designed prospective studies are needed to establish the effect of psychotherapy on disabling depression.

Surgeon attitudes toward nonphysician screening of low back or low back-related leg pain patients referred for surgical assessment: a survey of Canadian spine surgeons.

STUDY DESIGN: Questionnaire survey. OBJECTIVE: To explore spine surgeons' attitudes toward the involvement of nonphysician clinicians (NPCs) to screen patients with low back or low back-related leg pain referred for surgical assessment. SUMMARY OF BACKGROUND DATA: Although the utilization of physician assistants is common in several healthcare systems, the attitude of spine surgeons toward the independent assessment of patients by NPCs remains uncertain. METHODS: We administered a 28-item survey to all 101 surgeon members of the Canadian Spine Society, which inquired about demographic variables, patient screening efficiency, typical wait times for both assessment and surgery, important components of low back-related complaints history and examination, indicators for assessment by a surgeon, and attitudes toward the use of NPCs to screen patients with low back and leg pain referred for elective surgical assessment. RESULTS: Eighty-five spine surgeons completed our survey, for a response rate of 84.1%. Most respondents (77.6%) were interested in working with an NPC to screen patients with low back-related complaints referred for elective surgical assessment. Perception of suboptimal wait time for consultation and poor screening efficiency for surgical candidates were associated with greater surgeon interest in an NPC model of care. We achieved majority consensus regarding the core components for a low back-related complaints history and examination, and findings that would support surgical assessment. A majority of respondents (75.3%) agreed that they would be comfortable not assessing patients with low back-related complaints referred to their practice if indications for surgery were ruled out by an NPC. CONCLUSION: The majority of Canadian spine surgeons were open to an NPC model of care to assess and triage nonurgent or emergent low back-related complaints. Clinical trials to establish the effectiveness and acceptance of an NPC model of care by all stakeholders are urgently needed.

Assessment and implication of prognostic imbalance in randomized controlled trials with a binary outcome--a simulation study.

BACKGROUND: Chance imbalance in baseline prognosis of a randomized controlled trial can lead to over or underestimation of treatment effects, particularly in trials with small sample sizes. Our study aimed to (1) evaluate the probability of imbalance in a binary prognostic factor (PF) between two treatment arms, (2) investigate the impact of prognostic imbalance on the estimation of a treatment effect, and (3) examine the effect of sample size (n) in relation to the first two objectives. METHODS: We simulated data from parallel-group trials evaluating a binary outcome by varying the risk of the outcome, effect of the treatment, power and prevalence of the PF, and n. Logistic regression models with and without adjustment for the PF were compared in terms of bias, standard error, coverage of confidence interval and statistical power. RESULTS: For a PF with a prevalence of 0.5, the probability of a difference in the frequency of the PF≥5% reaches 0.42 with 125/arm. Ignoring a strong PF (relative risk = 5) leads to underestimating the strength of a moderate treatment effect, and the underestimate is independent of n when n is >50/arm. Adjusting for such PF increases statistical power. If the PF is weak (RR = 2), adjustment makes little difference in statistical inference. Conditional on a 5% imbalance of a powerful PF, adjustment reduces the likelihood of large bias. If an absolute measure of imbalance ≥5% is deemed important, including 1000 patients/arm provides sufficient protection against such an imbalance. Two thousand patients/arm may provide an adequate control against large random deviations in treatment effect estimation in the presence of a powerful PF. CONCLUSIONS: The probability of prognostic imbalance in small trials can be substantial. Covariate adjustment improves estimation accuracy and statistical power, and hence should be performed when strong PFs are observed.

A stochastic model for survival of early prostate cancer with adjustments for leadtime, length bias, and over-detection.

To compare the survival between screen-detected and clinically detected cancers, we applied a series of non-homogeneous stochastic processes to deal with leadtime, length bias, and over-detection by using full information on detection modes obtained from the Finnish randomized controlled trial for prostate cancer screening. The results show after 9-year follow-up the hazard ratio of prostate cancer death for screen-detected cases against clinically detected cases increased from 0.24 (95% CI: 0.16-0.35) without correction for these biases, to 0.76 after correction for leadtime and length biases, and finally to 1.03 (95% CI: 0.79-1.33) for a further adjustment for over-detection. Adjustment for leadtime and length bias but no over-detection led to a 24% reduction in prostate cancer death as a result of prostate-specific antigen test. The further calibration of over-detection indicates no gain in survival of screen-detected prostate cancers (excluding over-detected case as stayer considered in the mover-stayer model) as compared with the control group in the absence of screening that is considered as the mover. However, whether the model assumption on over-detection is robust should be validated with other data sets and longer follow-up.

Development and validation of an instrument to predict functional recovery in tibial fracture patients: the Somatic Pre-Occupation and Coping (SPOC) questionnaire.

OBJECTIVE: To explore the role of patients' beliefs in their likelihood of recovery from severe physical trauma. METHODS: We developed and validated an instrument designed to capture the impact of patients' beliefs on functional recovery from injury: the Somatic Pre-Occupation and Coping (SPOC) questionnaire. At 6-weeks postsurgical fixation, we administered the SPOC questionnaire to 359 consecutive patients with operatively managed tibial shaft fractures. We constructed multivariable regression models to explore the association between SPOC scores and functional outcome at 1 year as measured by return to work and Short Form-36 (SF-36) physical component summary and mental component summary scores. RESULTS: In our adjusted multivariable regression models that included preinjury SF-36 scores, SPOC scores at 6 weeks postsurgery accounted for 18% of the variation in SF-36 physical component summary scores and 18% of SF-36 mental component summary scores at 1 year. In both models, 6-week SPOC scores were a far more powerful predictor of functional recovery than age, gender, fracture type, smoking status, or the presence of multitrauma. Our adjusted analysis found that for each 14-point increment in SPOC score at 6 weeks (14 chosen on the basis of half a standard deviation of the mean SPOC score), the odds of returning to work at 1 year decreased by 40% (odds ratio, 0.60; 95% confidence interval, 0.50-0.73). CONCLUSION: The SPOC questionnaire is a valid measurement of illness beliefs in patients with tibial fracture and is highly predictive of their long-term functional recovery. Future research should explore if these results extend to other trauma populations and if modification of unhelpful illness beliefs is feasible and would result in improved functional outcomes.

Economic evaluation of reamed versus unreamed intramedullary nailing in patients with closed and open tibial fractures: results from the study to prospectively evaluate reamed intramedullary nails in patients with tibial fractures (SPRINT).

INTRODUCTION: Recently, results from the large, randomized study to prospectively evaluate reamed intramedullary nails in patients with tibial fractures (SPRINT) trial suggested a benefit for reamed intramedullary nail insertion in patients with closed tibial shaft fractures largely based on cost-neutral autodynamizations and a potential advantage for unreamed intramedullary nailing in open fractures. We performed an economic evaluation to compare resource use and effectiveness of reamed and unreamed intramedullary nailing using a cost-utility analysis. METHODS: We calculated quality-adjusted life years (QALYs) for each patient from a self-administered health utility index 3 questionnaire for the first 12 months following the intramedullary nailing. A convenience sample of 235 SPRINT patients provided data on costs associated with health care resource utilization. All costs are reported in Canadian dollars for the 2008 financial year. RESULTS: We found incremental effects of -0.017 (95% confidence interval [CI] -0.021-0.058) and -0.002 (95% CI -0.060-0.062) QALYs for patients treated with reamed compared with unreamed intramedullary nails in closed and open fractures, respectively. The incremental costs for reamed compared with unreamed intramedullary nailing were $51 Canadian dollars (95% CI -$2298-$2400) in closed tibial fractures and $2546 Canadian dollars (95%CI -$1773-$6864) in open tibial fractures. Unreamed nailing dominated reamed nailing for both closed and open tibial fractures; however, the cost and the utility results had high variability. CONCLUSION: Our economic analysis from a governmental perspective suggests small differences in both cost and effectiveness with large uncertainty between reamed and unreamed intramedullary nailing.

Quality of care in for-profit and not-for-profit nursing homes: systematic review and meta-analysis.

OBJECTIVE: To compare quality of care in for-profit and not-for-profit nursing homes. DESIGN: Systematic review and meta-analysis of observational studies and randomised controlled trials investigating quality of care in for-profit versus not-for-profit nursing homes. RESULTS: A comprehensive search yielded 8827 citations, of which 956 were judged appropriate for full text review. Study characteristics and results of 82 articles that met inclusion criteria were summarised, and results for the four most frequently reported quality measures were pooled. Included studies reported results dating from 1965 to 2003. In 40 studies, all statistically significant comparisons (P<0.05) favoured not-for-profit facilities; in three studies, all statistically significant comparisons favoured for-profit facilities, and the remaining studies had less consistent findings. Meta-analyses suggested that not-for-profit facilities delivered higher quality care than did for-profit facilities for two of the four most frequently reported quality measures: more or higher quality staffing (ratio of effect 1.11, 95% confidence interval 1.07 to 1.14, P<0.001) and lower pressure ulcer prevalence (odds ratio 0.91, 95% confidence interval 0.83 to 0.98, P=0.02). Non-significant results favouring not-for-profit homes were found for the two other most frequently used measures: physical restraint use (odds ratio 0.93, 0.82 to 1.05, P=0.25) and fewer deficiencies in governmental regulatory assessments (ratio of effect 0.90, 0.78 to 1.04, P=0.17). CONCLUSIONS: This systematic review and meta-analysis of the evidence suggests that, on average, not-for-profit nursing homes deliver higher quality care than do for-profit nursing homes. Many factors may, however, influence this relation in the case of individual institutions.

Use of both Short Musculoskeletal Function Assessment questionnaire and Short Form-36 among tibial-fracture patients was redundant.

OBJECTIVE: To compare the Short Musculoskeletal Function Assessment Dysfunction Index (SMFA DI) and the Short Form-36 Physical Component Summary (SF-36 PCS) scores among patients undergoing operative management of tibial fractures. STUDY DESIGN AND SETTING: Between July 2000 and September 2005, we enrolled 1,319 skeletally mature patients with open or closed fractures of the tibial shaft that were managed with intramedullary nailing. Patients were asked to complete the SMFA Questionnaire and SF-36 at discharge and 3, 6, and 12 months post-surgical fixation. RESULTS: The SMFA DI and SF-36 PCS scores were highly correlated at 3, 6, and 12 months post-surgical fixation. The difference in the mean standardized change scores for SMFA DI and SF-36 PCS, from 3 to 12 months post-surgical fixation, was not statistically significant. Both the SMFA DI and SF-36 PCS scores were able to discriminate between healed and nonhealed tibial fractures at 3, 6, and 12 months postsurgery. CONCLUSION: In patients with tibial-shaft fractures, the SMFA DI offered no significant advantages over the SF-36 PCS score. These results, along with the usefulness of SF-36 for comparing populations, recommend the SF-36 for assessing physical function in studies of patients with tibial fractures.

Low-back pain definitions in occupational studies were categorized for a meta-analysis using Delphi consensus methods.

OBJECTIVE: To determine which literature-based definitions of low back pain (LBP) could be combined to produce sufficiently similar sets for use in a meta-analysis. STUDY DESIGN AND SETTING: A group of six international experts participated in an e-mail-administered Delphi process. Literature-based LBP definitions were preliminarily classified into 14 sets within four outcome types: pathology, symptoms and care-seeking, functional limitations, and participation. Experts independently rated their level of agreement that each outcome definition belonged in its assigned set using a seven-point Likert scale. After each round, results were synthesized and revised classifications were fed back to the experts who were asked to consider them before rerating the outcome definitions. RESULTS: The experts completed three Delphi rounds and reached consensus on the categorization of 115/119 (97%) of the outcome definitions. There were 20 final sets of outcomes identified: three sets of pathology outcomes, two sets each of functional limitation and participation outcomes, and 13 sets of symptom and care-seeking outcomes. CONCLUSIONS: In a research area that currently lacks uniformly accepted definitions of outcomes, we successfully used a Delphi consensus process to reach substantial agreement on combinable LBP outcomes that would be combinable for a meta-analysis.

Effect of a clinical pathway to reduce hospitalizations in nursing home residents with pneumonia: a randomized controlled trial.

CONTEXT: Nursing home residents with pneumonia are frequently hospitalized. Such transfers may be associated with multiple hazards of hospitalization as well as economic costs. OBJECTIVE: To assess whether using a clinical pathway for on-site treatment of pneumonia and other lower respiratory tract infections in nursing homes could reduce hospital admissions, related complications, and costs. DESIGN, SETTING, AND PARTICIPANTS: A cluster randomized controlled trial of 680 residents aged 65 years or older in 22 nursing homes in Hamilton, Ontario, Canada. Nursing homes began enrollment between January 2, 2001, and April 18, 2002, with the last resident follow-up occurring July 4, 2005. Residents were eligible if they met a standardized definition of lower respiratory tract infection. INTERVENTIONS: Treatment in nursing homes according to a clinical pathway, which included use of oral antimicrobials, portable chest radiographs, oxygen saturation monitoring, rehydration, and close monitoring by a research nurse, or usual care. MAIN OUTCOME MEASURES: Hospital admissions, length of hospital stay, mortality, health-related quality of life, functional status, and cost. RESULTS: Thirty-four (10%) of 327 residents in the clinical pathway group were hospitalized compared with 76 (22%) of 353 residents in the usual care group. Adjusting for clustering of residents in nursing homes, the weighted mean reduction in hospitalizations was 12% (95% confidence interval [CI], 5%-18%; P = .001). The mean number of hospital days per resident was 0.79 in the clinical pathway group vs 1.74 in the usual care group, with a weighted mean difference of 0.95 days per resident (95% CI, 0.34-1.55 days; P = .004). The mortality rate was 8% (24 deaths) in the clinical pathway group vs 9% (32 deaths) in the usual care group, with a weighted mean difference of 2.9% (95% CI, -2.0% to 7.9%; P = .23). There were no significant differences between the groups in health-related quality of life or functional status. The clinical pathway resulted in an overall cost savings of US 1016 dollars per resident (95% CI, 207 dollars-1824 dollars) treated. CONCLUSION: Treating residents of nursing homes with pneumonia and other lower respiratory tract infections with a clinical pathway can result in comparable clinical outcomes, while reducing hospitalizations and health care costs. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00157612.

Interval estimation and optimal design for the within-subject coefficient of variation for continuous and binary variables.

BACKGROUND: In this paper we propose the use of the within-subject coefficient of variation as an index of a measurement's reliability. For continuous variables and based on its maximum likelihood estimation we derive a variance-stabilizing transformation and discuss confidence interval construction within the framework of a one-way random effects model. We investigate sample size requirements for the within-subject coefficient of variation for continuous and binary variables. METHODS: We investigate the validity of the approximate normal confidence interval by Monte Carlo simulations. In designing a reliability study, a crucial issue is the balance between the number of subjects to be recruited and the number of repeated measurements per subject. We discuss efficiency of estimation and cost considerations for the optimal allocation of the sample resources. The approach is illustrated by an example on Magnetic Resonance Imaging (MRI). We also discuss the issue of sample size estimation for dichotomous responses with two examples. RESULTS: For the continuous variable we found that the variance stabilizing transformation improves the asymptotic coverage probabilities on the within-subject coefficient of variation for the continuous variable. The maximum like estimation and sample size estimation based on pre-specified width of confidence interval are novel contribution to the literature for the binary variable. CONCLUSION: Using the sample size formulas, we hope to help clinical epidemiologists and practicing statisticians to efficiently design reliability studies using the within-subject coefficient of variation, whether the variable of interest is continuous or binary.

Mortality predictions in the intensive care unit: comparing physicians with scoring systems.

OBJECTIVE: Risk-prediction models offer potential advantages over physician predictions of outcomes in the intensive care unit (ICU). Our systematic review compared the accuracy of ICU physicians' and scoring system predictions of ICU or hospital mortality of critically ill adults. DATA SOURCE: MEDLINE (1966-2005), CINAHL (1982-2005), Ovid Healthstar (1975-2004), EMBASE (1980-2005), SciSearch (1980-2005), PsychLit (1985-2004), the Cochrane Library (Issue 1, 2005), PubMed "related articles," personal files, abstract proceedings, and reference lists. STUDY SELECTION: We considered all studies that compared physician predictions of ICU or hospital survival of critically ill adults to an objective scoring system, computer model, or prediction rule. We excluded studies if they focused exclusively on the development or economic evaluation of a scoring system, computer model, or prediction rule. DATA EXTRACTION AND ANALYSIS: We independently abstracted data and assessed study quality in duplicate. We determined summary receiver operating characteristic curves and areas under the summary receiver operating characteristic curves+/-se and summary diagnostic odds ratios. DATA SYNTHESIS: We included 12 observational studies of moderate methodological quality. The area under the summary receiver operating characteristic curves for seven studies was 0.85+/-0.03 for physician predictions compared with 0.63+/-0.06 for scoring system predictions (p=.002). Physicians' summary diagnostic odds ratios derived from the area under the summary receiver operating characteristic curves were significantly higher (12.43; 95% confidence interval 5.47, 27.11) than scoring systems' summary diagnostic odds ratios (2.25; 95% confidence interval 0.78, 6.52, p=.001). Combined results of all 12 studies indicated that physicians predict mortality more accurately than do scoring systems: ratio of diagnostic odds ratios (95% confidence interval) 1.92 (1.19, 3.08) (p=.007). CONCLUSIONS: Observational studies suggest that ICU physicians discriminate between survivors and nonsurvivors more accurately than do scoring systems in the first 24 hrs of ICU admission. The overall accuracy of both predictions of patient mortality was moderate, implying limited usefulness of outcome prediction in the first 24 hrs for clinical decision making.

Intra-class correlation estimates for assessment of vitamin A intake in children.

In many community-based surveys, multi-level sampling is inherent in the design. In the design of these studies, especially to calculate the appropriate sample size, investigators need good estimates of intra-class correlation coefficient (ICC), along with the cluster size, to adjust for variation inflation due to clustering at each level. The present study used data on the assessment of clinical vitamin A deficiency and intake of vitamin A-rich food in children in a district in India. For the survey, 16 households were sampled from 200 villages nested within eight randomly-selected blocks of the district. ICCs and components of variances were estimated from a three-level hierarchical random effects analysis of variance model. Estimates of ICCs and variance components were obtained at village and block levels. Between-cluster variation was evident at each level of clustering. In these estimates, ICCs were inversely related to cluster size, but the design effect could be substantial for large clusters. At the block level, most ICC estimates were below 0.07. At the village level, many ICC estimates ranged from 0.014 to 0.45. These estimates may provide useful information for the design of epidemiological studies in which the sampled (or allocated) units range in size from households to large administrative zones.

Three day versus five day treatment with amoxicillin for non-severe pneumonia in young children: a multicentre randomised controlled trial.

OBJECTIVE: To assess the efficacy of three days versus five days of treatment with oral amoxicillin for curing non-severe pneumonia in children. DESIGN: Randomised, double blind, placebo controlled multicentre trial. SETTING: Outpatient departments of seven referral hospitals in India. PARTICIPANTS: 2188 children aged 2-59 months, 1095 given three days of treatment and 1093 given five days. INTERVENTION: Oral amoxicillin 31-54 mg/kg/day in three divided doses. MAIN OUTCOME MEASURES: Treatment failure: defined as development of chest indrawing, convulsions, drowsiness, or inability to drink at any time; respiratory rate above age specific cut points on day 3 or later; or oxygen saturation by pulse oximetry < 90% on day 3. RESULTS: The clinical cure rates with three days and five days of treatment were 89.5% and 89.9%, respectively (absolute difference 0.4 (95% confidence interval--2.1 to 3.0)). Adherence to treatment regimen was 94% and 85% for three day and five day treatments, respectively. Loss to follow up was 5.4% by day 5. There were no deaths, 41 hospitalisations, and 36 minor adverse reactions. There were 225 (10.3%) clinical failures and 106 (5.3%) relapses, and rates were similar in both treatments. At enrollment, 513 (23.4%) children tested positive for respiratory syncytial virus, and Streptococcus pneumoniae and Haemophilus influenzae were isolated from the nasopharynx in 878 (40.4%) and 496 (22.8%) children, respectively. Clinical failure was associated with isolation of respiratory syncytial virus (adjusted odds ratio 1.95 (95% confidence interval 1.0 to 3.8)), excess respiratory rate of > 10 breaths/minute (2.89 (1.83 to 4.55)), and non-adherence with treatment at day 5 (11.57 (7.4 to 18.0)). CONCLUSIONS: Treatment with oral amoxicillin for three days was as effective as for five days in children with non-severe pneumonia.

Adjunctive human papillomavirus testing in the 2-year follow-up of women with low-grade cervical cytologic abnormalities: a randomized trial and economic evaluation.

CONTEXT: Although human papillomavirus (HPV) testing may aid in managing low-grade abnormality on screening cervical cytology, patient compliance with repeat testing programs requires consideration. OBJECTIVES: To determine effectiveness and costs of repeated Papanicolaou (Pap) test and oncogenic HPV testing for detecting cervical intraepithelial neoplasia 2 or 3. DESIGN: We conducted a randomized controlled trial of combined Pap test and cervical HPV testing by Hybrid Capture 1 test compared with Pap test alone; tests were performed every 6 months for up to 2 years. The study end point was colposcopic examination performed on all women at 2 years, or earlier if an HPV test was positive or if a Pap test showed high-grade squamous intraepithelial lesion. SETTING: Sixty-six community family practices. PARTICIPANTS: Two hundred fifty-seven women with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion on screening cervical cytology. MAIN OUTCOME MEASURES: Detection of histologically confirmed cervical intraepithelial neoplasia 2 or 3, fully allocated costs, and loss to follow-up. RESULTS: Combined Pap test and HPV testing detected 11 (100%) of 11 cases of cervical intraepithelial neoplasia 2/3, whereas Pap test alone detected 7 (63.6%) of these 11 cases (P =.14); corresponding specificities were 39 (46.4%) of 84 and 45 (71.4%) of 63 (P =.005). The cost-effectiveness ratio was Can $4456 per additional case of high-grade cervical intraepithelial neoplasia. Sixty-nine (26.8%) of the 257 women (24.6% combined group vs 29.1% Pap test only group, P =.41) defaulted from testing or from colposcopy when referred with an abnormal result. CONCLUSIONS: Combined testing was more costly but may detect more cases of cervical intraepithelial neoplasia 2/3 than Pap test alone. However, poor adherence limits usefulness of a management strategy that requires repeated follow-up.